Since the onset of the acquired immunodeficiency syndrome (AIDS) pandemic in 1981, the human immunodeficiency virus (HIV) has spread exponentially throughout the world. HIV is neuroinvasive (with invasion occurring early during the course of the infection) and neurovirulent (causing neuropathy, myopathy, myelopathy, and dementia), but it is not neurotrophic. The virus is rarely isolated from neurones either in the peripheral or central nervous system (CNS).
Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. The mechanisms of demyelination in HIV infection could be due to lesions directly related to infections of the nervous system by HIV itself, opportunistic infections and lymphomas secondary to cell-mediated immunodeficiency, other general and systemic complications of HIV. Here, we present these two cases with features of noninfective cerebellar demyelination that were found to have HIV infection.
A 49-year-old male patient was admitted to our department with subacute onset of imbalance while walking with bilateral tremors for 20 days. Patient also complained of slurring of speech for 15 days. There was no history of fever or headache. He had no motor or sensory deficit and no bladder or bowel involvement. There was no history of seizures or visual disturbances. He had a history of recurrent oral ulceration for 1 year. He had allergy to quinolones and sulpha drugs. He had normal appetite and sleep.
On CNS examination, he had scanning speech with ataxic gait. Cranial nerves were normal. He had bilateral cerebellar signs without any power loss. Fundus examination showed no abnormality.
His complete blood count was normal. Erythrocyte sedimentation rate (ESR) was 35mm at 1 hour. Rheumatoid factor, C-reactive protein, and anti-nuclear antibody were done to rule out collagen vascular disease; all testswere negative. Magnetic resonance imaging (MRI) of the brain showed symmetrical areas of signal alteration in bilateral middle cerebellar peduncles, cerebellar white matter, and parts of pons appearing hypointense on T1 and hyperintense on T2 without restricted diffusion and without cerebellar or brainstem atrophy [Figure 1], [Figure 2], [Figure 3], [Figure 4]. Lesions showed no contrast enhancement on gadolinium administration. Test for HIV 1 was positive on three different enzyme-linked immunosorbent assay (ELISA) methods. CD4 count was 400/cu.mm. Cerebrospinal fluid (CSF) examination showed raised protein (83mg) with normal glucose (54mg), cells (<5) with negative CSF ADA and India ink preparation. CSF examination for atypical cells was negative. Polymerase chain reaction (PCR) for John Cunningham JC virus was negative.
Because there was no contrast enhancement and CSF was negative for atypical cells, CNS lymphoma was less likely. Considering acute demyelination, he was treated with intravenous methylprednisolone 1g per day for 5 days with clinical improvement. Ataxia decreased and patient could walk independently after 4 weeks of admission. He was referred to ART clinic for further evaluation and follow-up.
A 26-year-old male, taxi driver by occupation, was admitted to our department with complains of positional vertigo and imbalance while walking for 20 days. He also complained of slurring of speech for 20 days. He had 4–5 episodes of nonprojectile vomiting one day prior to admission. He had no headache, seizures, or any visual disturbances at admission. He had no preceding cough, cold, diarrhoea, or skin rash. There was no history of weight loss, night sweats, or anorexia.
On examination, his vitals were stable. His cognitive functions were normal. His speech was scanning type with bilateral horizontal nystagmus. Power was grade 5 in all limbs with normal sensory examination. He had bilateral cerebellar signs with broad based ataxic gait.
His routine laboratory investigations were normal. MRI brain showed geographic areas of altered signal intensities in bilateral cerebellar white matter, appearing hypointense on T1 and hyperintense on T2 without contrast enhancement or any mass effect [Figure 5]. His CSF examination revealed elevated proteins (71mg%), with normal sugar (58mg%) and cell count(<5/cu.mm.). CSF ADA, India ink, and VDRL were negative. JC virus PCR was negative. He was found positive for HIV1 by three different ELISA methods with CD4 count of 456/cu.mm.
Considering acute demyelination, he was initially started on intravenous methylprednisolone 1 g per day for 5 days with significant clinical improvement. He was referred to the ART clinic for registration and follow-up.
Demyelinating CNS disorders in HIV are rare and are due to acute perivenous inflammatory leukoencephalopathy, presenting either as acute hemorrhagic leukoencephalopathy, acute demyelinating perivenous encephalitis, or acute multiple sclerosis-like leukoencephalopathy or PML. True demyelination may result from various mechanisms which are not well understood. These include lesions directly related to infection of the nervous tissue by HIV, opportunistic infections and lymphomas secondary to the cell-mediated immunodeficiency, and changes due to other general or systemic complications of AIDS. The pathogenesis of myelin destruction is unclear. Direct infection of neurons or glial cells has never been demonstrated. Indirect immunopathologic, toxic, metabolic, or vascular mechanisms secondary to infection of monocytes/macrophages are more likely.
Progressive multifocal leukoencephalopathy (PML) is demyelinating disease of CNS that is caused by JC virus (JCV), a polyomavirus. Before highly active antiretroviral treatment HAART, 5% of AIDS patients developed PML with CD4 counts usually below 100/mm. The clinical presentation is subacute with a progressive hemiparesis, hemianopia, or ataxia. Cognitive dysfunction usually occurs with focal neurological signs. Cortical involvement may occasionally result in dysphasia and seizures. The parieto-occipital and frontal lobes are most commonly affected. The affected areas are low signal on T1-weighted images and hyperintense on T2-weighted sequences without mass effect.
Diagnosis is done by isolation of JCV-DNA in the CSF by PCR with a sensitivity of 75% and almost complete specificity. It may be necessary to repeat the CSF examination in PCR negative cases (raising the yield to 85%) before considering stereotactic brain biopsy.
Cerebellar disorders associated with HIV infection are typically due to discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Tagliati et al. reported 10 patients with syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection. Engsig et al. found that 25 (53%) of 47 PML patients had lesions involving the cerebellum and/or brainstem that were visualized radiographically. In a study done by Deshpande and Patnaik, out of 4 HIV patients having demyelination, 1 had cerebellar demyelination. Nakamura et al. reported a patient presenting with subacute-onset cerebellar syndrome who was then diagnosed to be HIV positive.
Both of our patients presented with subacute-onset bilateral cerebellar syndrome. Considering MRI findings and clinical improvement with steroids, demyelination was more likely. Both patients later turned out to be HIV positive. Both were not willing to undergo a brain biopsy. We could not establish the exact pathogenesis of cerebellar demyelination in our patients. However, HIV infection should be considered as an etiology in the clinical setting of subacute ataxia, particularly in a young or immunocompromised patient.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]